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In silico Studies on the Interaction between Mpro and PLpro From SARS-CoV-2 and Ebselen, its Metabolites and Derivatives.
Nogara, Pablo Andrei; Omage, Folorunsho Bright; Bolzan, Gustavo Roni; Delgado, Cássia Pereira; Aschner, Michael; Orian, Laura; Teixeira Rocha, João Batista.
Afiliação
  • Nogara PA; Departamento de Bioquímica e Biologia Molecular, Universidade Federal de Santa Maria (UFSM), Santa Maria, 97105-900, RS, Brazil.
  • Omage FB; Departamento de Bioquímica e Biologia Molecular, Universidade Federal de Santa Maria (UFSM), Santa Maria, 97105-900, RS, Brazil.
  • Bolzan GR; Departamento de Bioquímica e Biologia Molecular, Universidade Federal de Santa Maria (UFSM), Santa Maria, 97105-900, RS, Brazil.
  • Delgado CP; Departamento de Bioquímica e Biologia Molecular, Universidade Federal de Santa Maria (UFSM), Santa Maria, 97105-900, RS, Brazil.
  • Aschner M; Department of Molecular Pharmacology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY, 10461, USA.
  • Orian L; Dipartimento di Scienze Chimiche, Università degli Studi di Padova, Via Marzolo 1, 35131, Padova, Italy.
  • Teixeira Rocha JB; Departamento de Bioquímica e Biologia Molecular, Universidade Federal de Santa Maria (UFSM), Santa Maria, 97105-900, RS, Brazil.
Mol Inform ; 40(8): e2100028, 2021 08.
Article em En | MEDLINE | ID: mdl-34018687
The COVID-19 pandemic caused by the SARS-CoV-2 has mobilized scientific attention in search of a treatment. The cysteine-proteases, main protease (Mpro) and papain-like protease (PLpro) are important targets for antiviral drugs. In this work, we simulate the interactions between the Mpro and PLpro with Ebselen, its metabolites and derivatives with the aim of finding molecules that can potentially inhibit these enzymes. The docking data demonstrate that there are two main interactions between the thiol (-SH) group of Cys (from the protease active sites) and the electrophilic centers of the organoselenium molecules, i. e. the interaction with the carbonyl group (O=C… SH) and the interaction with the Se moiety (Se… SH). Both interactions may lead to an adduct formation and enzyme inhibition. Density Functional Theory (DFT) calculations with Ebselen indicate that the energetics of the thiol nucleophilic attack is more favorable on Se than on the carbonyl group, which is in accordance with experimental data (Jin et al. Nature, 2020, 582, 289-293). Therefore, organoselenium molecules should be further explored as inhibitors of the SARS-CoV-2 proteases. Furthermore, we suggest that some metabolites of Ebselen (e. g. Ebselen diselenide and methylebselenoxide) and derivatives ethaselen and ebsulfur should be tested in vitro as inhibitors of virus replication and its proteases.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Inibidores de Proteases / Azóis / Proteínas da Matriz Viral / Compostos Organosselênicos / Proteases Semelhantes à Papaína de Coronavírus / SARS-CoV-2 / Tratamento Farmacológico da COVID-19 Limite: Humans Idioma: En Revista: Mol Inform Ano de publicação: 2021 Tipo de documento: Article País de afiliação: Brasil País de publicação: Alemanha

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Inibidores de Proteases / Azóis / Proteínas da Matriz Viral / Compostos Organosselênicos / Proteases Semelhantes à Papaína de Coronavírus / SARS-CoV-2 / Tratamento Farmacológico da COVID-19 Limite: Humans Idioma: En Revista: Mol Inform Ano de publicação: 2021 Tipo de documento: Article País de afiliação: Brasil País de publicação: Alemanha